| #606685 | ||||||||||||
| CARDIOMYOPATHY, DILATED, 1L; CMD1L | ||||||||||||
| Phenotype Gene Relationships | ||||||||||||
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| Phenotypic Series | ||||||||||||
| TEXT | ||||||||||||
| A number sign (#) is used with this entry because this form of dilated cardiomyopathy is caused by mutations in the gene encoding delta-sarcoglycan (SGCD; 601411). | ||||||||||||
| Description | ||||||||||||
| Dilated cardiomyopathy, a disorder characterized by cardiac dilation and reduced systolic function, represents an outcome of a heterogeneous group of inherited and acquired disorders. For background and phenotypic information on dilated cardiomyopathy, see CMD1A (115200). | ||||||||||||
| Molecular Genetics | ||||||||||||
| Cardiomyopathy in the hamster is a model of human hereditary cardiomyopathy and is divided into hypertrophic cardiomyopathy (HCM; BIO 14.6 strain) and dilated cardiomyopathy (DCM; TO-2 strain) inbred sublines, both of which descended from the same ancestor and are due to mutations in the gene encoding delta-sarcoglycan (Sakamoto et al., 1997; Nigro et al., 1997). Hypothesizing that DCM is a disease of the cytoskeleton and sarcolemma, Tsubata et al. (2000) focused on candidate genes whose products are found in these structures. They screened the human SGCD gene in patients with DCM by SSCP analysis and DNA sequencing. Mutations affecting the secondary structure of SGCD were identified in 1 family (S151A; 601411.0006) and in 2 sporadic cases (K238del; 601411.0005). Immunofluorescence analysis of myocardium from 1 of these patients demonstrated significant reduction in SGCD staining. No skeletal muscle disease occurred in any of these patients. In a consanguineous family of Arab origin, in which homozygosity for an A131P mutation in the SGCD gene (601411.0007) had been identified in 3 sibs with limb-girdle muscular dystrophy type 2F (LGMD2F; 601287), Bauer et al. (2009) also identified heterozygosity for the S151A mutation in 7 unaffected family members, 4 of whom were compound heterozygous for the S151A and A131P mutations. Comprehensive clinical and cardiac investigation in all 4 of the compound heterozygous family members revealed no signs of cardiomyopathy or limb-girdle muscular dystrophy. Bauer et al. (2009) questioned the pathologic relevance of the S151A variant, and of the SGCD gene itself, in dilated cardiomyopathy. | ||||||||||||
| REFERENCES | ||||||||||||
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